Abstract
Many persons find it intuitive that being friends with someone with immoral beliefs is wrong as such. I contest this claim, instead I argue that there is nothing necessarily wrong with such ...friendships. In coming to this conclusion I examine a number of arguments, including two of the most notable contributions put forward by Mason (2021) and Isserow (2018), that attempt to elucidate the wrongness involved in such friendships and find they do not successfully do so. I conclude by offering some arguments as to why such friendships are not necessarily wrong.
Household Demand for Water in Rural Kenya Wagner, Jake; Cook, Joseph; Kimuyu, Peter
Environmental & resource economics,
12/2019, Volume:
74, Issue:
4
Journal Article
Peer reviewed
To expand and maintain water supply infrastructure in rural regions of developing countries, planners and policymakers need better information on the preferences of households who might use the ...sources. Using data from 387 households in rural Kenya, we model source choice and water demand using a discrete-continuous (linked) demand model. We find that households are sensitive to the price, proximity, taste, and availability in choosing among sources, but are not sensitive to other source qualities including color, health risk, and risk of conflict. Estimates of the value of time implied by our model suggest that households value time spent collecting water at one third of unskilled wages. We use the linked demand framework to estimate own-price elasticities in the rural setting. These estimates range between − 0.13 and − 1.33, with a mean of − 0.56, and are consistent with other elasticity estimates from small and large cities.
Abstract
ImmuneSpace is a data repository and analysis platform of the Human Immunology Project Consortium (HIPC), a multi-center collaborative effort to characterize the status of the immune system ...in different populations under diverse stimulations and disease states. This ongoing effort has generated large amounts of varied high-throughput, high-dimensional immunological data. ImmuneSpace directly extracts data from ImmPort -- the central NIAID database, and further standardizes it for meta-analysis and reporting, making it ready to be explored using state-of-art visualization and analysis tools. ImmuneSpace will act as a central immunological hub, allowing experimentalists, statisticians, and bioinformaticians to freely retrieve, explore and compare data across assays and across studies generated within and outside of HIPC. We present a selection of multi-cohort analyses using standardized gene expression and flow cytometry data sets across multiple studies identifying novel baseline predictors of vaccine efficacy across a variety of pathogens.
Manuscript 1 is titled, "Household demand for water in rural Kenya", and is coauthored with Joseph Cook and Peter Kimuyu. In this manuscript we use a household survey from 387 households in rural ...Kenya to model source choice and water demand using a discrete-continuous (linked) demand model. We find that households are sensitive to the price, proximity, taste, and availability in choosing among sources, but are not sensitive to other source qualities including color, health risk, and risk of conflict. We use the linked demand framework to estimate own-price elasticities in the rural setting. These range between -0.13 and -1.33, with a mean of -0.56, consistent with other estimates from small and large cities. Manuscript 2 is titled, "Energy efficiency information asymmetries in the rental housing market", and is a solo work. In this manuscript I exploit the variation in payment-status (who pays the energy bill), to estimate the effect of information asymmetries on the adoption of efficient (Energy Star rated) technologies in the U.S. rental housing market. Results show that, contrary to previous findings, landlords who pay their tenant's energy bill are no more likely to install energy efficient technologies, suggesting that information asymmetries play a nominal role in the adoption of efficient technologies in the rental housing market. Manuscript 3 is titled, "A linked-demand model to characterize multiple discrete-continuous demand", and is coauthored with Joseph Cook. In this manuscript we develop a reduced form multiple discrete-continuous demand model. Using this model we analyze weekly household demand for water in rural Ethiopia, and characterize four important aspects of demand: (1) total household water demand, (2) source-specific household demand, (3) aggregate water demand at each source, and (4) household preferences across source attributes. Results show that households value water quality, proximity and price in choosing which sources to collect from. Average own-price elasticity estimates from the aggregate demand analysis are found to be -0.18, and are consistent with other own-price elasticity estimates from middle- and low-income countries.
Pulmonary hypertension (PH) is a progressive disease that causes high patient mortality. With limited hemodynamic reserve, many PH patients require maintenance IV infusion medications to maintain ...their activities of daily living. One common delivery method for this targeted therapy is through a Remodulin® (treprostinil) pump. When presenting for emergent evaluation, decompensating PH patients have a broad differential diagnosis including pump failure. PH patients are at a high risk of poor patient outcomes given the difficulty in recognizing PH-specific symptoms and unique aspects of their management. Therefore, learners will benefit from participating in an immersive simulation-based PH patient scenario in a safe learning environment. Here, we present a simulated scenario of a decompensating PH patient on a Remodulin® pump.
Introduction: The intratumoral heterogeneity of Acute Myeloid Leukemia (AML) and other hematologic malignancies presents a challenge in developing effective single-agent targeted treatments. ...Furthermore, the emergence of genetically heterogeneous subclones leading to relapse suggests that effective therapies associated with discrete genotypes may require drug combinations, each of which modulates distinct pathways. In addition, microenvironmental rescue signals as well as tumor-intrinsic feedback pathways in AML and other hematologic malignancy subsets will necessitate combinatorial therapy approaches. Towards the goal of identifying new therapeutic combinations for AML and other hematologic malignancies, we assessed the sensitivity of primary patient samples to various drug combinations using an ex vivo functional platform.
Methods: We have previously screened over 1000 primary patient specimens against a panel of single-agent small-molecule inhibitors. Using these historical drug sensitivity data, we ranked drugs by their IC50, and used these rankings to assemble an initial panel (1) of 44 drug combinations consisting primarily of kinase inhibitors with non-overlapping pathways. Primary patient samples (n = 74) with various hematologic malignancies were assessed for sensitivities to these combinations by culturing cells in the presence of fixed molar concentrations of the drugs over a dose series. Sensitivity was assessed by a viability assay on day 3 using a tetrazolium reagent. IC50 values for samples sensitive to a combination were sorted according to disease type and compared to those for each single agent to derive an index of effectiveness. Based on data from panel 1, we generated a second panel (2) consisting of 44 drug combinations, including new combinations of kinase inhibitors as well as combinations of drugs from different classes, such as bromodomain inhibitors, BH3 mimetics, proteasome inhibitors, IDH1/2 inhibitors coupled with kinase inhibitors. Primary patient samples (n = 78) were assessed for sensitivities to these combinations.
Results: The performance of drug combinations across AML, ALL, CLL, CML or other MDS/MPN specimens are displayed in a heat map (Figure 1) representing the sensitivities of each drug combination relative to either of the single agents comprising that combination (the combination IC50 divided by the lowest single agent IC50 is our combination ratio). For each combination, we then compared the combination ratio of each individual specimen to the median combination ratio across all specimens tested, and cases with a combination ratio value less than 20% of the median were considered hypersensitive to that combination. We calculated the percentage of cases that were sensitive to each combination within the diagnostic subsets of AML, ALL, CLL, CML, and MDS/MPN and subsets with the most frequent sensitivity to a drug combination are indicated on the heat map (<20%, dark red; 20-50%, dark pink; 50-80%, light pink; and >80%, white).
Combinations of two kinase inhibitors that included the p38MAPK inhibitor, doramapimod, were generally more effective on AML and CLL samples than other diagnostic subsets (panel 1). For CLL sample, combinations including midostaurin and either alisertib, ruxolitinib or sorafenib were particularly effective. Among combinations on panel 2, doramapimod coupled with an apoptosis inducer (ABT-199) exhibited broad efficacy on AML samples. In addition, combinations with the bromodomain inhibitor, JQ1, or the BH3 mimetic, ABT-199, were more broadly effective across diagnostic subsets than many of the kinase-kinase pairs tested. To validate the apparent synergies observed with patient samples, we tested selected combinations on AML-derived cell lines and observed synergies, which were supported with combination indices derived by the Chou-Talalay method.
Conclusions: These data suggest that specific drug combinations formed either with two kinase inhibitors or with two compounds from different drug classes are effective in a patient-specific manner with enrichment for certain drug pairs within specific diagnostic subsets. While a secondary evaluation is necessary to validate the initial observation of sensitivity, linking this methodology with genetic attributes for patient samples will identify effective combinations of targeted agents and add therapeutic options for AML treatment.
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Pandya:Microsoft: Employment, Equity Ownership. Bolosky:Microsoft: Employment, Equity Ownership. Druker:Oregon Health & Science University: Patents & Royalties; Henry Stewart Talks: Patents & Royalties; CTI Biosciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Research Funding; Aptose Therapeutics, Inc (formerly Lorus): Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; McGraw Hill: Patents & Royalties; Leukemia & Lymphoma Society: Membership on an entity's Board of Directors or advisory committees, Research Funding; MolecularMD: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Roche TCRC, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Millipore: Patents & Royalties; AstraZeneca: Consultancy; Oncotide Pharmaceuticals: Research Funding; Cylene Pharmaceuticals: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Fred Hutchinson Cancer Research Center: Research Funding; ARIAD: Research Funding; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sage Bionetworks: Research Funding. Tyner:Incyte: Research Funding; Janssen Pharmaceuticals: Research Funding; Constellation Pharmaceuticals: Research Funding; Array Biopharma: Research Funding; Aptose Biosciences: Research Funding.
The preoperative identification of osteoporosis in the spine surgery population is of crucial importance. Limitations associated with dual-energy x-ray absorptiometry, such as access and reliability, ...have prompted the search for alternative methods to diagnose osteoporosis. The Hounsfield Unit(HU), a readily available measure on computed tomography, has garnered considerable attention in recent years as a potential diagnostic tool for reduced bone mineral density. However, the optimal threshold settings for diagnosing osteoporosis have yet to be determined.
We selected studies that included comparison of the HU(index test) with dual-energy x-ray absorptiometry evaluation(reference test). Data quality was assessed using the standardised QUADAS-2 criteria. Studies were characterised into 3 categories, based on the threshold of the index test used with the goal of obtaining a high sensitivity, high specificity or balanced sensitivity-specificity test.
9 studies were eligible for meta-analysis. In the high specificity group, the pooled sensitivity was 0.652 (95% CI 0.526 – 0.760), specificity 0.795 (95% CI 0.711 – 0.859) and diagnostic odds ratio was 6.652 (95% CI 4.367 – 10.133). In the high sensitivity group, the overall pooled sensitivity was 0.912 (95% CI 0.718 – 0.977), specificity was 0.67 (0.57 – 0.75) and diagnostic odds ratio was 19.424 (5.446 – 69.275). In the balanced sensitivity-specificity group, the overall pooled sensitivity was 0.625 (95% CI 0.504 – 0.732), specificity was 0.914 (0.823 – 0.960) and diagnostic odds ratio was 14.880 (7.521 – 29.440). Considerable heterogeneity existed throughout the analysis.
In conclusion, the HU is a clinically useful tool to aide in the diagnosis of osteoporosis. However, the heterogeneity seen in this study warrants caution in the interpretation of results. We have demonstrated the impact of differing HU threshold values on the diagnostic ability of this test. We would propose a threshold of 135 HU to diagnose OP. Future work would investigate the optimal HU cut-off to differentiate normal from low bone mineral density.
A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease.
In this phase 1-2 randomized, double-blind, ...placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months.
A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio vaccine vs. placebo, 1.53; 95% confidence interval CI, 0.66 to 3.55; vaccine efficacy, -53%; 95% CI, -255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, -66%; 95% CI, -250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×10
IU per milliliter and 1804.93×10
IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups.
In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.).
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